丝裂霉素C不同给药间隔对人类膀胱癌细胞杀伤、生存及耐药性的研究

A pharmacodynamic study of intervals of Mitomycin C treatment on human bladder cancer cell line in vitro

目的研究丝裂霉素 C(MMC)不同给药间隔与药物对膀胱癌细胞的杀伤、凋亡及耐药性产生之间的关系。方法分别间隔24、48、72和96h,用 MMC 处理 BIU-87细胞,2 h/次,共5次,MTT 法检测细胞毒作用,Western blot 分析 p53、bcl-2、bax 及 p170的表达。结果间隔24、48、72、96 h 给药,IC_(50)分别为4.41、0.71、2.83、4.31、6.16μg/ml;间隔24 h 给药,BIU87细胞 p53、bcl-2表达明显下调,bcl-2/bax 比值显著减小;间隔48、72和96 h 给药,p53、bcl-2的表达及 bcl-2/bax 的比值无明显改变;间隔24 h 给药5次,均未见 p170表达,间隔48、72、96 h 给药,p170表达逐渐增强。结论 MMC 的给药间隔与药物对人类膀胱癌细胞的杀伤作用以及癌细胞的凋亡及耐药性的产生密切相关,膀胱内灌注化疗的给药间隔也是影响疗效的重要因素。

Objective To study the relationship between the intervals of Mitomycin C treatment and cytotoxicity, apoptosis and drug resistance for bladder cancer cells.Methods The bladder transitional cell cancer line BIU-87 was treated for two hours every time for five times with intervals of 24, 48, 72 and 96 hours respectively.Cytotoxicity was measured by MTT.p53,bcl-2,Bax and p170 expression were analyzed by Western blot.Results The IC_(50)(μg/ml)were 4.41,0.71,2.83,4.51and 6.16 with treatment intervals of 24, 48, 72 and 96 hours respectively, p53 and bcl-2 were significantly down-regulated and bcl-2/Bax was re- duced at 24 hour treatment interval but not changed at 48,72 and 96 hour intervals,p170 was not detected at 24 hour treatment interval but increasingly expressed at 48,72 and 96 hours intervals.Conclusion The in- terval of Mitomycin C treatment is closely related with cytotoxieity and apoptosis and drug resistance of blad- der cancer cells.The intervals of intravesical instillations may play an important role in the effect of chemotherapy.